Dystroglycan contributes to the formation of multiple dystrophin-like complexes in brain

被引:62
作者
Moukhles, H
Carbonetto, S
机构
[1] McGill Univ, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada
[2] Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada
关键词
dystroglycan; dystrophin; mdx(3cv) mice; postsynaptic density;
D O I
10.1046/j.1471-4159.2001.00466.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In muscle, dystrophin anchors a complex of proteins at the cell surface which Includes alpha -dystroglycan, beta -dystroglycan, syntrophins and dystrobrevins. Mutations in the dystrophin gene lead to muscular dystrophy and mental retardation. In contrast to muscle, little is known about the localization and the molecular interactions of dystrophin and dystrophin associated proteins (DAPs) in brain. In the present study, we show that alpha -dystroglycan and dystrophin are localized to large neurones in cerebral cortex, hippocampus, cerebellum and spinal cord. Furthermore, we show that dystroglycan is a member of three distinct dystrophin-containing complexes. Two of these complexes contain syntrophin and both dystrophin and syntrophin are enriched in post-synaptic densities. These data suggest that dystrophin and DAPs may have a role in the organization of CNS synapses, Interestingly, the enrichment for syntrophin in post-synaptic densities is not affected in mice mutant for all dystrophin isoforms. Thus in the brain, unlike in muscle, the association of syntrophin with dystrophin is not crucial for the DAP complex which suggests that it may be associated with other proteins.
引用
收藏
页码:824 / 834
页数:11
相关论文
共 56 条
[1]   Different dystrophin-like complexes are expressed in neurons and glia [J].
Blake, DJ ;
Hawkes, R ;
Benson, MA ;
Beesley, PW .
JOURNAL OF CELL BIOLOGY, 1999, 147 (03) :645-657
[2]   The neurobiology of Duchenne muscular dystrophy:: learning lessons from muscle? [J].
Blake, DJ ;
Kröger, S .
TRENDS IN NEUROSCIENCES, 2000, 23 (03) :92-99
[3]   Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains [J].
Brenman, JE ;
Chao, DS ;
Gee, SH ;
McGee, AW ;
Craven, SE ;
Santillano, DR ;
Wu, ZQ ;
Huang, F ;
Xia, HH ;
Peters, MF ;
Froehner, SC ;
Bredt, DS .
CELL, 1996, 84 (05) :757-767
[4]   NITRIC-OXIDE SYNTHASE COMPLEXED WITH DYSTROPHIN AND ABSENT FROM SKELETAL-MUSCLE SARCOLEMMA IN DUCHENNE MUSCULAR-DYSTROPHY [J].
BRENMAN, JE ;
CHAO, DS ;
XIA, HH ;
ALDAPE, K ;
BREDT, DS .
CELL, 1995, 82 (05) :743-752
[5]   ROLE FOR DYSTROPHIN-ASSOCIATED GLYCOPROTEINS AND UTROPHIN IN AGRIN-INDUCED ACHR CLUSTERING [J].
CAMPANELLI, JT ;
ROBERDS, SL ;
CAMPBELL, KP ;
SCHELLER, RH .
CELL, 1994, 77 (05) :663-674
[6]   The dynamics of dystroglycan [J].
Chamberlain, J .
NATURE GENETICS, 1999, 23 (03) :256-258
[7]   In vitro expressed dystrophin fragments do not associate with each other [J].
Chan, YM ;
Kunkel, LM .
FEBS LETTERS, 1997, 410 (2-3) :153-159
[8]   THE RAT-BRAIN POSTSYNAPTIC DENSITY FRACTION CONTAINS A HOMOLOG OF THE DROSOPHILA DISKS-LARGE TUMOR SUPPRESSOR PROTEIN [J].
CHO, KO ;
HUNT, CA ;
KENNEDY, MB .
NEURON, 1992, 9 (05) :929-942
[9]   DISTRIBUTION OF ALPHA-DYSTROGLYCAN DURING EMBRYONIC NERVE-MUSCLE SYNAPTOGENESIS [J].
COHEN, MW ;
JACOBSON, C ;
GODFREY, EW ;
CAMPBELL, KP ;
CARBONETTO, S .
JOURNAL OF CELL BIOLOGY, 1995, 129 (04) :1093-1101
[10]   Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses [J].
Côté, PD ;
Moukhles, H ;
Lindenbaum, M ;
Carbonetto, S .
NATURE GENETICS, 1999, 23 (03) :338-342